Developmental aspects of language processing: fMRI of verbal fluency in children and adults

We examined developmental differences, in location and extent of fMRI language activation maps, between adults and children while performing a semantic fluency task. We studied 29 adults and 16 children with echo planar imaging BOLD fMRI at 1.5 T using covert semantic verbal fluency (generation of words to categories compared to rest) using a block design. Post task testing was administered to assess performance. Individual data were analyzed with an a priori region of interest approach from t maps (t = 4) and asymmetry indices (AI). Group studies were analyzed using SPM 99 (Wellcome, UK; fixed effect, corrected P < 0.0001). We found no significant differences in location or laterality of activation between adults and children for a semantic verbal fluency task. Adults activated more pixels than children in left inferior frontal gyrus and left middle frontal gyrus, but AIs were the similar across ages (r(2) < 0.09). Extent or laterality of activation was not affected by performance (r(2) < 0.15). The brain areas that process semantic verbal fluency are similar in children and adults. The laterality of activation does not change appreciably with age and appears to be strongly lateralized by age 7 years.     

首发精神分裂症患者的功能磁共振初步研究

目的 利用血氧水平依赖性(blood oxygenation level-dependent,BOLD)功能磁共振成像(functional magnetic resonance imaging,fMRI)技术探讨首发精神分裂症患者治疗前后认知功能激发图像的特点。方法 13例首发精神分裂症患者入组,用利培酮或氯丙嗪治疗后9例患者复查fMRI。以词语流畅性作业(verbal fluency task,VF)作为任务,采用Block设计,用梯度回波-平面回波成像(GRE-EPI)序列采集数据,经工作站处理后获功能图像。结果 (1)VF激活受试者的额叶(前额叶)、顶叶及颞叶皮层;(2)复查的9例受试者中,7例激活增强,2例激活减弱;(3)治疗后激活增强的7例受试者的双侧额上、中、下回激活有增加趋势,而双侧颞上、中、下回激活有减少趋势(P>0.05);但左额叶背外侧面治疗后的激活明显强于治疗前(P=0.032)。结论 BOLD-fMRI可用于研究人脑的高级认知功能。首发精神分裂症患者治疗前后脑功能图像有明显变化,提示认知缺陷症状是可以治疗的。     

Functional MR evaluation of temporal and frontal language dominance compared with the Wada test

OBJECTIVE: To evaluate the reliability of temporal and frontal functional MRI (fMRI) activation for the assessment of language dominance, as compared with the Wada test. PATIENTS AND METHODS: Ten patients with temporal lobe epilepsy were studied using blood oxygen level dependent fMRI and echoplanar imaging (1.5-T). Three tasks were used: semantic verbal fluency, covert sentence repetition, and story listening. Data were analyzed using pixel by pixel autocorrelation and cross-correlation. fMRI laterality indices were defined for several regions of interest as the ratio (L - R)/(L + R), L being the number of activated voxels in the left hemisphere and R in the right hemisphere. Wada laterality indices were defined as the difference in the percentages of errors in language tests between left and right carotid injections. RESULTS: Semantic verbal fluency: The asymmetry of frontal activation was correlated with Wada laterality indices. The strongest correlation was observed in the precentral/middle frontal gyrus/inferior frontal sulcus area. Story listening: The asymmetry of frontal, but not temporal, activation was correlated with Wada laterality indices. Covert sentence repetition: No correlation was observed. CONCLUSIONS: There was a good congruence between hemispheric dominance for language as assessed with the Wada test and fMRI laterality indices in the frontal but not in the temporal lobes. The story listening and the covert sentence repetition tasks increased the sensitivity of detection of posterior language sites that may be useful for brain lesion surgery.     

The neurodevelopmental differences of increasing verbal working memory demand in children and adults

Working memory (WM) – temporary storage and manipulation of information in the mind – is a key component of cognitive maturation, and structural brain changes throughout development are associated with refinements in WM. Recent functional neuroimaging studies have shown that there is greater activation in prefrontal and parietal brain regions with increasing age, with adults showing more refined, localized patterns of activations. However, few studies have investigated the neural basis of verbal WM development, as the majority of reports examine visuo-spatial WM.We used fMRI and a 1-back verbal WM task with six levels of difficulty to examine the neurodevelopmental changes in WM function in 40 participants, twenty-four children (ages 9–15 yr) and sixteen young adults (ages 20–25 yr). Children and adults both demonstrated an opposing system of cognitive processes with increasing cognitive demand, where areas related to WM (frontal and parietal regions) increased in activity, and areas associated with the default mode network decreased in activity. Although there were many similarities in the neural activation patterns associated with increasing verbal WM capacity in children and adults, significant changes in the fMRI responses were seen with age. Adults showed greater load-dependent changes than children in WM in the bilateral superior parietal gyri, inferior frontal and left middle frontal gyri and right cerebellum. Compared to children, adults also showed greater decreasing activation across WM load in the bilateral anterior cingulate, anterior medial prefrontal gyrus, right superior lateral temporal gyrus and left posterior cingulate. These results demonstrate that while children and adults activate similar neural networks in response to verbal WM tasks, the extent to which they rely on these areas in response to increasing cognitive load evolves between childhood and adulthood.     

Imaging language networks before and after anterior temporal lobe resection: results of a longitudinal fMRI study

Purpose: Anterior temporal lobe resection (ATLR) controls seizures in up to 70% of patients with intractable temporal lobe epilepsy (TLE) but, in the language dominant hemisphere, may impair language function, particularly naming. Functional reorganization can occur within the ipsilateral and contralateral hemispheres. We investigated reorganization of language in left‐hemisphere–dominant patients before and after ATLR; whether preoperative functional magnetic resonance imaging (fMRI) predicts postoperative naming decline; and efficiency of postoperative language networks. Methods: We studied 44 patients with TLE due to unilateral hippocampal sclerosis (24 left) on a 3T GE‐MRI scanner. All subjects performed language fMRI and neuropsychological testing preoperatively and again 4 months after left or right ATLR. Key Findings: Postoperatively, individuals with left TLE had greater bilateral middle/inferior frontal fMRI activation and stronger functional connectivity from the left inferior/middle frontal gyri to the contralateral frontal lobe than preoperatively, and this was not observed in individuals with right TLE. Preoperatively, in left and right TLE, better naming correlated with greater preoperative left hippocampal and left frontal activation for verbal fluency (VF). In left TLE, stronger preoperative left middle frontal activation for VF was predictive of greater decline in naming after ATLR. Postoperatively, in left TLE with clinically significant naming decline, greater right middle frontal VF activation correlated with better postoperative naming. In patients without postoperative naming decline, better naming correlated with greater activation in the remaining left posterior hippocampus. In right TLE, naming ability correlated with left hippocampal and left and right frontal VF activation postoperatively. Significance: In left TLE, early postoperative reorganization to the contralateral frontal lobe suggests multiple systems support language function. Postoperatively, ipsilateral recruitment involving the posterior hippocampal remnant is important for maintaining language, and reorganization to the contralateral hemisphere is less effective. Preoperative left middle frontal activation for VF was predictive of naming decline in left TLE after ATLR.     

注意缺陷/多动障碍工作记忆的bold-功能磁共振成像研究

目的应用bold-功能磁共振成像(bold-fMRI)技术来研究注意缺陷/多动障碍(AD/HD)患者的工作记忆。并探讨使用哌醋甲酯1个月治疗前后AD/HD患者的脑部激活的改变情况。方法利用倒数n刺激模式(n-back)对7例AD/HD(注意缺陷为主型)和7名正常人进行blod-fMRI检查,对照研究AD/HD患者在工作记忆时涉及的各脑区的激活情况。结果AD/HD组治疗后的1-back任务较治疗前1-back任务在右额下回和右额中回激活明显,二者有显著性差异(P<0.05);AD/HD组在治疗后的2-back任务较治疗前2-back任务在左额下回和左顶叶后下部激活明显(P<0.05)。正常组的1-back任务与患者组治疗前的1-back任务比较没有显著性差异,正常组的2-back任务与患者组治疗前2-back任务比较在左额下回和左顶叶后下部激活明显(P<0.05)。结论AD/HD障碍患者存在执行功能方面的缺陷,AD/HD患者的语义性工作记忆缺损可能与前额叶和顶叶的功能缺陷有关。     

FMRI lateralization of expressive language in children with cerebral lesions

PURPOSE: Lateralization of language function is crucial to the planning of surgery in children with frontal or temporal lobe lesions. We examined the utility of functional magnetic resonance imaging (fMRI) as a determinant of lateralization of expressive language in children with cerebral lesions. METHODS: fMRI language lateralization was attempted in 35 children (29 with epilepsy) aged 8-18 years with frontal or temporal lobe lesions (28 left hemisphere, five right hemisphere, two bilateral). Axial and coronal fMRI scans through the frontal and temporal lobes were acquired at 1.5 Tesla by using a block-design, covert word-generation paradigm. Activation maps were lateralized by blinded visual inspection and quantitative asymmetry indices (hemispheric and inferior frontal regions of interest, at p<0.001 uncorrected and p<0.05 Bonferroni corrected). RESULTS: Thirty children showed significant activation in the inferior frontal gyrus. Lateralization by visual inspection was left in 21, right in six, and bilateral in three, and concordant with hemispheric and inferior frontal quantitative lateralization in 93% of cases. Developmental tumors and dysplasias involving the inferior left frontal lobe had activation overlying or abutting the lesion in five of six cases. fMRI language lateralization was corroborated in six children by frontal cortex stimulation or intracarotid amytal testing and indirectly supported by aphasiology in a further six cases. In two children, fMRI language lateralization was bilateral, and corroborative methods of language lateralization were left. Neither lesion lateralization, patient handedness, nor developmental versus acquired nature of the lesion was associated with language lateralization. Involvement of the left inferior or middle frontal gyri increased the likelihood of atypical language lateralization. CONCLUSIONS: fMRI lateralizes language in children with cerebral lesions, although caution is needed in interpretation of individual results.     

Neural correlates of working memory performance in adolescents and young adults with dyslexia

Behavioral studies indicate deficits in phonological working memory (WM) and executive functioning in dyslexics. However, little is known about the underlying functional neuroanatomy. In the present study, neural correlates of WM in adolescents and young adults with dyslexia were investigated using event-related functional magnetic resonance imaging (fMRI) and a parametric verbal WM task which required the manipulation of verbal material. Dyslexics were not significantly slower than controls; however, they were less accurate with the highest WM demand. The functional analysis excluded incorrectly performed and omitted trials, thus controlling for potential activation confounds. Compared with control subjects, both increased and decreased activation of the prefrontal cortex were found in the dyslexic group. Dyslexics showed significantly more activation than controls with increasing WM demand in the left superior frontal gyrus (BA 8), as well as in the inferior frontal gyrus including Broca's area (BA 44) and its right homologue. Less activation was found in the middle frontal gyrus (BA 6) and in the superior parietal cortex (BA 7). A positive correlation between activation of prefrontal regions and verbal WM performance (as measured by digit span backwards) was found only in the dyslexic group. Accuracy deficits at the highest cognitive demand during the verbal WM task and the digit span backwards suggest that manipulation rather than maintenance is selectively impaired in dyslexics. The fMRI data provide further evidence for functional differences in cortical regions associated with language processing and executive function in subjects with dyslexia.     

正常人词语流畅性作业的脑功能磁共振成像研究

目的 利用功能磁共振成像(fMRI)技术探讨词语流畅性作业的脑功能定位。方法对18名健康志愿者进行词语流畅性作业的fMRI检查,fMRI用梯度回波-平面回波成像序列采集数据,经工作站处理后获功能图像。结果 经Fisher精确检验法,健康志愿者的双侧额上回、双侧额中回、右侧额下回及右侧扣带回的激活脑区计数,与理想激活脑区计数的差异均无显著性(P>0.05),其余脑区激活计数的差异均有显著性(P<0.05)。结论 双侧额叶背外侧及右侧额叶腹外侧可能参与长时记忆的提取过程,其中额叶背外侧可能参与核查及管理工作,而额叶腹外侧可能参与搜寻特异目标的过程。     

Temporo-frontal activation during phonological processing predicts gains in arithmetic facts in young children

Behavioral studies have shown discrepant results regarding the role of phonology in predicting math gains. The objective of this study was to use fMRI to study the role of activation during a rhyming judgment task in predicting behavioral gains on math fluency, multiplication, and subtraction skill. We focused within the left middle/superior temporal gyrus and left inferior frontal gyrus, brain areas associated with the storage of phonological representations and with their access, respectively. We ran multiple regression analyses to determine whether activation predicted gains in the three math measures, separately for younger (i.e. 10 years old) and older (i.e 12 years old) children. Results showed that activation in both temporal and frontal cortex only predicted gains in fluency and multiplication skill, and only for younger children. This study suggests that both temporal and frontal cortex activation during phonological processing are important in predicting gains in math tasks that involve the retrieval of facts that are stored as phonological codes in memory. Moreover, these results were specific to younger children, suggesting that phonology is most important in the early stages of math development. When the math task involved subtractions, which relies on quantity representations, phonological processes were not important in driving gains.     

Neuroimaging of valence decisions in children and adults

To date, the neural underpinnings of affective components in language processing in children remain largely unknown. To fill this gap, the present study examined behavioural and neural correlates of children and adults performing the same auditory valence decision task with an event-related fMRI paradigm. Based on previous findings in adults, activations in anterior and posterior cingulate cortex, orbitofrontal cortex and left inferior frontal gyrus were expected for both positive and negative valence categories. Recent behavioural findings on valence decisions showed similar ratings and reaction time patterns in children and adults. This finding was successfully replicated in the present study. On a neural level, our analysis of affective language processing showed activations in regions associated with both semantic (superior and middle temporal and frontal) and affective (anterior and posterior cingulate, orbitofrontal and inferior frontal, insula and amygdala) processing. Neural activations in children and adults were systematically different in explicit affective word processing. In particular, adults showed a more distributed semantic network activation while children recruited additional subcortical structures.     

Genetic variation in the schizophrenia‐risk gene neuregulin 1 correlates with brain activation and impaired speech production in a verbal fluency task in healthy individuals

Impaired performance in verbal fluency tasks is an often replicated finding in schizophrenia. In functional neuroimaging studies, this dysfunction has been linked to signal changes in prefrontal and temporal areas. Since schizophrenia has a high heritability, it is of interest whether susceptibility genes for the disorder, such as NRG1, modulate verbal fluency performance and its neural correlates. Four hundred twenty‐nine healthy individuals performed a semantic and a lexical verbal fluency task. A subsample of 85 subjects performed an overt semantic verbal fluency task while brain activation was measured with functional magnetic resonance imaging (MRI). NRG1 (SNP8NRG221533; rs35753505) status was determined and correlated with verbal fluency performance and brain activation. For the behavioral measure, there was a linear effect of NRG1 status on semantic but not on lexical verbal fluency. Performance decreased with number of risk‐alleles. In the fMRI experiment, decreased activation in the left inferior frontal and the right middle temporal gyri as well as the anterior cingulate gyrus was correlated with the number of risk‐alleles in the semantic verbal fluency task. NRG1 genotype does influence language production on a semantic level in conjunction with the underlying neural systems. These findings are in line with results of studies in schizophrenia and may explain some of the cognitive and brain activation variation found in the disorder. More generally, NRG1 might be one of several genes that influence semantic language capacities. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Compensatory brain activation in children with attention deficit/hyperactivity disorder during a simplified Go/No-go task

Given that a number of recent studies have shown attenuated brain activation in prefrontal regions in children with ADHD, it has been recognized as a disorder in executive function. However, fewer studies have focused exclusively on the compensatory brain activation in ADHD. The present study objective was to investigate the compensatory brain activation patterns during response inhibition (RI) processing in ADHD children. In this study, 15 ADHD children and 15 sex-, age-, and IQ-matched control children were scanned with a 3-T MRI equipment while performing a simplified letter Go/No-go task. The results showed more brain activation in the ADHD group compared with the control group, whereas the accuracy and reaction time of behavioral performance were the same. Children with ADHD did not activate the normal RI brain circuits, which are thought to be predominantly located in the right middle/inferior frontal gyrus (BA46/44), right inferior parietal regions (BA40), and pre-SMA(BA6), but instead, activated brain regions, such as the left inferior frontal cortex, the right inferior temporal cortex, the right precentral gyrus, the left postcentral gyrus, the inferior occipital cortex, the middle occipital cortex, the right calcarine, the right hippocampus, the right midbrain, and the cerebellum. Our conclusion is that children with ADHD tend to compensatorily use more posterior and diffusive brain regions to sustain normal RI function.     

Effects of generation mode in fMRI adaptations of semantic fluency: paced production and overt speech

Verbal fluency is a widely used neuropsychological paradigm. In fMRI implementations, conventional unpaced (self-paced) versions are suboptimal due to uncontrolled timing of responses, and overt responses carry the risk of motion artifact. We investigated the behavioral and neurofunctional effects of response pacing and overt speech in semantic category-driven word generation. Twelve right-handed adults (8 females), ages 21-37 were scanned in four conditions each: paced-overt, paced-covert, unpaced-overt, and unpaced-covert. There was no significant difference in the number of exemplars generated between overt versions of the paced and unpaced conditions. Imaging results for category-driven word generation overall showed left-hemispheric activation in inferior frontal cortex, premotor cortex, cingulate gyrus, thalamus, and basal ganglia. Direct comparison of generation modes revealed significantly greater activation for the paced compared to unpaced conditions in right superior temporal, bilateral middle frontal, and bilateral anterior cingulate cortex, including regions associated with sustained attention, motor planning, and response inhibition. Covert (compared to overt) conditions showed significantly greater effects in right parietal and anterior cingulate, as well as left middle temporal and superior frontal regions. We conclude that paced overt paradigms are useful adaptations of conventional semantic fluency in fMRI, given their superiority with regard to control over and monitoring of behavioral responses. However, response pacing is associated with additional non-linguistic effects related to response inhibition, motor preparation, and sustained attention.     

fMRI auditory language differences between dyslexic and able reading children

During fMRI, dyslexic and control boys completed auditory language tasks (judging whether pairs of real and/or pseudo words rhymed or were real words) in 30 s 'on' conditions alternating with a 30 s 'off' condition (judging whether tone pairs were same). During phonological judgment, dyslexics had more activity than controls in right than left inferior temporal gyrus and in left precentral gyrus. During lexical judgment, dyslexics were less active than controls in bilateral middle frontal gyrus and more active than controls in left orbital frontal cortex. Individual dyslexics were reliably less active than controls in left insula and left inferior temporal gyrus. Dyslexic and control children differ in brain activation during auditory language processing skills that do not require reading.     

Anomalous prefrontal-subcortical activation in familial pediatric bipolar disorder: a functional magnetic resonance imaging investigation

BACKGROUND: The neurobiological features of pediatric bipolar disorder (BD) are largely unknown. Children and adolescents with BD may be important to study with functional neuroimaging techniques because of their unique status of early-onset BD and high familial loading for the disorder. Neuroimaging studies of adults with BD have implicated the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in the development of this disorder. OBJECTIVES: To study children and adolescents with BD via functional magnetic resonance imaging using cognitive and affective tasks and to examine possible abnormalities in the DLPFC and ACC, as well as selected subcortical areas, in pediatric familial BD. DESIGN: We evaluated 12 male subjects aged 9 to 18 years with BD who had at least 1 parent with BD as well as 10 age- and IQ-matched healthy male controls. Stimulants were discontinued for at least 24 hours; other medications were continued. Subjects underwent functional magnetic resonance imaging at 3 T while performing a 2-back visuospatial working memory task and an affective task involving the visualization of positively, neutrally, or negatively valenced pictures. SETTING: An academic referral setting, drawing from the Bay Area of San Francisco, Calif. RESULTS: Compared with controls, for the visuospatial working memory task, subjects with BD had greater activation in several areas including the bilateral ACC, left putamen, left thalamus, left DLPFC, and right inferior frontal gyrus. Controls had greater activation in the cerebellar vermis. In viewing negatively valenced pictures, subjects with BD had greater activation in the bilateral DLPFC, inferior frontal gyrus, and right insula. Controls had greater activation in the right posterior cingulate gyrus. For positively valenced pictures, subjects with BD had greater activation in the bilateral caudate and thalamus, left middle/superior frontal gyrus, and left ACC, whereas controls had no areas of greater activation. CONCLUSIONS: Children and adolescents with BD may have underlying abnormalities in the regulation of prefrontal-subcortical circuits. Further functional magnetic resonance imaging studies of attention and mood with greater sample sizes are needed.     

Developmental and skill effects on the neural correlates of semantic processing to visually presented words

Functional magnetic resonance imaging (fMRI) was used to explore the neural correlates of semantic judgments to visual words in a group of 9- to 15-year-old children. Subjects were asked to indicate if word pairs were related in meaning. Consistent with previous findings in adults, children showed activation in bilateral inferior frontal gyri (Brodmann area [BA] 47, 45) and left middle temporal gyrus (BA 21). Words with strong semantic association elicited significantly greater activation in bilateral inferior parietal lobules (BA 40), suggesting stronger integration of highly related semantic features. By contrast, words with weak semantic association elicited greater activation in left inferior frontal gyrus (BA 45) and middle temporal gyrus (BA 21), suggesting more difficult feature search and more extensive access to semantic representations. We also examined whether age and skill explained unique variance in the patterns of activation. Increasing age was correlated with greater activation in left middle temporal gyrus (BA 21) and inferior parietal lobule (BA 40), suggesting that older children have more elaborated semantic representations and more complete semantic integration processes, respectively. Decreasing age was correlated with activation in right superior temporal gyrus (BA 22) and decreasing accuracy was correlated with activation in right middle temporal gyrus (BA 21), suggesting the engagement of ancillary systems in the right hemisphere for younger and lower-skill children.     

A functional magnetic resonance imaging study during sentence reading in Japanese dyslexic children

A functional magnetic resonance imaging (fMRI) study during Japanese 'kana' readings was performed on Japanese dyslexic children. Five dyslexic children (aged 9-12 years) and five healthy children (aged 9-11 years) were investigated. The fMRI examination was performed by getting these children to read sentences constructed from Japanese phonograms, 'kana', compared with staring at meaningless figures as a control task. All control subjects showed activation of the left middle temporal gyrus. In the dyslexic children, the activation of the middle temporal gyrus was rather vague. However, other distinctively activated regions were detected as follows: the bilateral occipital cortex in two dyslexics, the inferior part of the frontal regions in two other dyslexics, and both the bilateral occipital cortex and the inferior part of precentral gyrus in the remaining one. These results indicate compensatory management processes for the unskilled reading ability of dyslexic children. The present results were similar to previous ones for adult dyslexia with the Roman alphabet, and suggest that brain malfunction in dyslexia during the task of reading must be common despite differences in languages.